An Introduction to RNA Interference (RNAi) and Drug Development

Drugs based on RNA interference (RNAi) are believed by many to be
the next major class of human therapeutics. This potential has been
recognized with the 2006 Nobel Prize for Medicine awarded to Craig
Mello and Andrew Fire for their discovery of RNAi, and has resulted in
major investments in RNAi-based drug development by large
pharmaceutical and biotech companies. These investments include a
series of transformative drug discovery alliances considered to be
among the biggest in biotech history.

Recent breakthroughs in the understanding of the central
role for RNA in a variety of cellular mechanisms have further
facilitated the development of RNAi therapeutics.

The development of RNAi therapeutics has greatly benefited from an
unprecedented advancement of the basic science relating to the role of
RNA in an ever expanding spectrum of biological processes. While RNA
had long been regarded to merely facilitate gene expression as a
passive intermediate and structural component of the protein expression
apparatus – or operating in a 'messenger' capacity -- it is now clear
that RNA has many of the genetic, regulatory, and catalytic properties
formerly thought to be possessed only by DNA and proteins.

The original function of the RNAi mechanism, which still operates in
many invertebrates today, was that of a cellular RNA-based immune
system designed to ‘interfere’ with the uncontrolled production of
aberrant RNA molecules, which could be interpreted by the body as an
opportunistic viral infection. Like our natural adaptive immune
response, the RNAi mechanism is extremely specific in targeting these
RNA molecules. In fact, they are identified for degradation by
well-defined complementarity rules between the targeting small RNA and
target messenger RNA (mRNA).